{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T13:41:28Z","timestamp":1768225288218,"version":"3.49.0"},"reference-count":27,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T00:00:00Z","timestamp":1768003200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Cenobamate (CNB) is an anti-seizure medication (ASM) approved for the treatment of drug-resistant focal epilepsy in adults. Notwithstanding significant proof of efficacy, real-world pharmacokinetics (PK) data are lacking, particularly regarding sex-based variations and the effect of concomitant ASMs. This exploratory study aimed to investigate the PK profile of CNB in responder adults with drug-resistant focal epilepsy and assess potential relationship with concomitant ASMs and clinical variables. Methods: We enrolled 17 patients receiving add-on CNB. The concentration-to-dose ratio (C\/D), incremental slope (\u0394C\/\u0394D), and dose-to-concentration AUC were calculated. Enrolled individuals were stratified into three exposure clusters (low, medium, and high). Univariate ANOVA was used to explore associations between PK parameters, clinical variables and concomitant ASMs. Results: Sex appeared to be associated with AUC cluster classification (p = 0.026), showing females predominating in the high-exposure group. A nonlinear dose-concentration relationship emerged from the \u0394C\/\u0394D analysis, showing steeper slopes at low doses (12.5\u201350 mg), great variability at higher doses (100\u2013200 mg), and a negative slope in some individuals. Higher CNB concentrations were observed in patients co-treated with lacosamide, while concomitant topiramate was associated with lower exposure. Carbamazepine and valproate showed non-significant trends consistent with their known enzyme-inducing and inhibiting properties. Conclusions: PK of CNB appears highly variable and seems to be influenced by sex and concomitant ASMs. These findings highlight the importance of therapeutic drug monitoring and individualized titration strategies to optimize efficacy and safety in clinical practice. These results should be regarded as exploratory and hypothesis-generating due to the small and monocentric sample size and need to be confirmed in larger, multicenter cohorts.<\/jats:p>","DOI":"10.3390\/pharmaceutics18010092","type":"journal-article","created":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T10:25:23Z","timestamp":1768213523000},"page":"92","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Do Cenobamate Pharmacokinetics Change with Co-Administered Antiseizure Medications? An Exploratory Analysis of Responder Patients with Focal Drug-Resistant Epilepsy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5076-3220","authenticated-orcid":false,"given":"Bruno","family":"Charlier","sequence":"first","affiliation":[{"name":"Operative Unit of Clinical Pharmacology, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"},{"name":"Post-Graduate School in Clinical Pharmacology and Toxicology, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6066-7569","authenticated-orcid":false,"given":"Viviana","family":"Izzo","sequence":"additional","affiliation":[{"name":"Operative Unit of Clinical Pharmacology, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"},{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3129-1982","authenticated-orcid":false,"given":"Giovanni","family":"Assenza","sequence":"additional","affiliation":[{"name":"Research Unit of Neurology, Department of Medicine and Surgery, Universit\u00e0 Campus Bio-Medico di Roma, Via Alvaro del Portillo, 21, 00128 Roma, Italy"},{"name":"Operative Research Unit of Neurology, Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna Chiara","family":"Balsamo","sequence":"additional","affiliation":[{"name":"Operative Unit of Clinical Pharmacology, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"},{"name":"Post-Graduate School in Clinical Pharmacology and Toxicology, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia","family":"Cirillo","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Neurology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2724-8212","authenticated-orcid":false,"given":"Albino","family":"Coglianese","sequence":"additional","affiliation":[{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Salerno, Italy"},{"name":"Post-Graduate School in Clinical Pathology and Clinical Biochemistry, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1890-5409","authenticated-orcid":false,"given":"Carlo","family":"Di Bonaventura","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7384-3074","authenticated-orcid":false,"given":"Antonio","family":"Gambardella","sequence":"additional","affiliation":[{"name":"Department of Science of Health, School of Medicine, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"},{"name":"Neurologic Clinic, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3906-555X","authenticated-orcid":false,"given":"Emanuele","family":"Cerulli Irelli","sequence":"additional","affiliation":[{"name":"Department of Human Neurosciences, Sapienza University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudio","family":"Liguori","sequence":"additional","affiliation":[{"name":"Department of Systems Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Neurology Unit, University Hospital of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7756-6241","authenticated-orcid":false,"given":"Sandra","family":"Rufolo","sequence":"additional","affiliation":[{"name":"Operative Unit of Clinical Pharmacology, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"},{"name":"Post-Graduate School in Clinical Pathology and Clinical Biochemistry, University of Salerno, Baronissi, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-9245","authenticated-orcid":false,"given":"Ilaria","family":"Sammarra","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8235-9118","authenticated-orcid":false,"given":"Amelia","family":"Filippelli","sequence":"additional","affiliation":[{"name":"Operative Unit of Clinical Pharmacology, University Hospital \u201cSan Giovanni di Dio e Ruggi d\u2019Aragona\u201d, 84131 Salerno, Italy"},{"name":"Department of Medicine, Surgery and Dentistry \u201cScuola Medica Salernitana\u201d, University of Salerno, 84081 Salerno, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca Felicia","family":"Operto","sequence":"additional","affiliation":[{"name":"Neurologic Clinic, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"},{"name":"Department of Medical and Surgical Sciences, Institute of Neurology, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"},{"name":"Centre for Research in Unusual Infections, Epilepsy and Neuroscience (CRUISE), Science of Health Department, Magna Gr\u00e6cia University, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,10]]},"reference":[{"key":"ref_1","unstructured":"(2025, June 02). 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